• YAKHAK HOEJI
• /
• v.42 no.4
• /
• pp.345-352
• /
• 1998

Praecoxin A, an ellagitannin, purified from Alnus hirsuta var.microphlla was evaluated on the antitumor activity. Praecoxin A had the significant cytotoxicity to s ix tumor cell lines: human chronic myelogenous leukemia K-562, human promyelocytic leukemia HL-60, mouse leukemia P388, mouse lymphocytic leukemia L-1210, sarcoma-l8O, mouse lymphoma L5178Y except L-1210. And the most sensitive cell line was K-562 ($ED_{50}=2.43{\mu}g/ml$). The $ED_{50} of praecoxin A against HL-60, P388, L-1210, sarcoma7l8O and L5178Y were 6.28, 8.66, 10.00, 7.01, $9.32{\mu}g/ml$, respectively. Praecoxin A showed the increasing effect in life span by 36.8% on the 1st day after treatment of 10mg/kg in mice bearing sarcoma-180 tumor cells (ascitic form) via NCI (National Cancer Institute, U.S.A.) protocol in vivo assay. As a result, praecoxin A is considered to show the antitumor activity.

• Environmental Analysis Health and Toxicology
• /
• v.22 no.3
• /
• pp.263-269
• /
• 2007

Chitosan is a depolymerized and partially deacetylated derivative of chitin. We investigated the cytotoxicity of chitosan in cancer cell lines, such as P388, L1210, HCT-15, SK-HepG-1 and mouse splenocytes as a normal cell by MTT assay. To clarify whether chitosan enhances cytotoxicity of anticancer drugs, we also examined the cytotoxicity of combined treatment with chitosan and anticancer drugs, such as cisplatin, mitomycin C, and 5-fluorouracil in cancer cell lines in vitro. Chitosan ($37.5\;{\mu}g/mL,\;75\;{\mu}g/mL,\;112.5\;{\mu}g/mL,\;and\;150\;{\mu}g/mL$) showed concentration-dependent cytotoxicity in the cancer cell lines. In addition, chitosan showed relatively lower cytotoxicity in normal cells than in the cancer cell lines. Particularly, this trend was significant at high doses of chitosan, i.e. $112.5\;{\mu}g/mL,\;and\;150\;{\mu}g/mL$. Thus, these results suggest that chitosan may selectively induce the growth inhibition in cancer cell lines, compared to normal cells. Furthermore. the co-treatment of chitosan and anticancer drugs exhibited an apparant synergistic cytotoxicity in murine lymphoma cell lines, i.e. P388 and L1210 at $37.5\;{\mu}g/mL$ of chitosan rather than at $75\;{\mu}g/mL$ of chitosan, but such phenomenon could not be observed in solid tumor cell lines, i.e. HCT-15 and SK-HepG-1. However, chitosan did'nt reduced the cytotoxicity against normal mouse splenocytes induced by anticancer drugs. Therefore, it is concluded that the combination of chitosan and anticancer drugs might be useful for the cancer chemotherapy.

• Toxicological Research
• /
• v.30 no.3
• /
• pp.211-220
• /
• 2014

Resveratrol has received considerable attention as a polyphenol with various biological effects such as anti-inflammatory, anti-oxidant, anti-mutagenic, anti-carcinogenic, and cardioprotective properties. As part of the overall safety assessment of HS-1793, a novel resveratrol analogue free from the restriction of metabolic instability and the high dose requirement of resveratrol, we assessed genotoxicity in three in vitro assays: a bacterial mutation assay, a comet assay, and a chromosomal aberration assay. In the bacterial reverse mutation assay, HS-1793 did not increase revertant colony numbers in S. typhimurium strains (TA98, TA100, TA1535 and TA1537) or an E. coli strain (WP2 uvrA) regardless of metabolic activation. HS-1793 showed no evidence of genotoxic activity such as DNA damage on L5178Y $Tk^{+/-}$ mouse lymphoma cells with or without the S9 mix in the in vitro comet assay. No statistically significant differences in the incidence of chromosomal aberrations following HS-1793 treatment was observed on Chinese hamster lung cells exposed with or without the S9 mix. These results provide additional evidence that HS-1793 is non-genotoxic at the dose tested in three standard tests and further supports the generally recognized as safe determination of HS-1793 during early drug development.

• IMMUNE NETWORK
• /
• v.4 no.4
• /
• pp.216-223
• /
• 2004

Background: It is well known that IgA isotype switching is induced by $TGF-{\beta}1$. LPS-activated mouse normal B cells well differentiate into IgA secreting plasma cells under the influence of $TGF-{\beta}1$. Nevertheless, there are lots of difficulties in studying normal B cells in detail because it is not simple to obtain highly purified B cells, showing low reproducibility and transfection efficacy, moreover impossible to keep continuous culture. To overcome these obstacles, it is desperately needed to develop B cell line which acts like normal B cells. In the present study, we investigated whether CH12F3-2A lymphoma cells are appropriate for studying IgA isotype switching event. Methods: CH12F3-2A B cell line was treated with LPS and $TGF-{\beta}1$, then levels of germ-line (GL) transcripts were measured by RT-PCR, and $GL{\alpha}$ promoter activity was measured by luciferase assay. In addition, membrane IgA (mIgA) expression and IgA secretion were determined by FACS and ELISA, respectively. Results: $TGF-{\beta}1$, regardless of the presence of LPS, increased level of $GL{\alpha}$ transcripts but not $GL{\gamma}2b$ transcripts. However, IgA secretion was increased dramatically by co-stimulation of LPS and $TGF-{\beta}1$. Both mIgA and IgA secretion in the presence of $TGF-{\beta}1$ were further increased by over-expression of Smad3/4. Finally, $GL{\alpha}$ promoter activity was increased by $TGF-{\beta}1$. Conclusion: CH12F3-2A cell line acts quite similarly to the normal B cells which have been previously reported regarding IgA expression. Thus, CH12F3-2A lymphoma cell line appears to be adequate for the investigation of the mechanism(s) of IgA isotype switching at the cellular and molecular levels.

• Journal of the Korean Chemical Society
• /
• v.41 no.7
• /
• pp.357-361
• /
• 1997

8-Azaxanthine (1), 3-${\beta}$-D-ribofuranosyl-8-azaxanthine (2), 3-${\beta}$-D-ribofuranosyl-8-azaxanthine-5'-monophosphate (3), and 3-${\beta}$-D-ribofuranosyl-8-azaxanthine-5'-(3-pyridinylcarbonyl)monophosphate (4) were synthesized. The in vitro antitumor activities of the synthesized compounds against P388 mouse leukemia, FM3A mammary carcinoma, and U937 human histiocytic lymphoma cells were determined by MTT assay. 2 with unnatural N-3 and C-1' glycoside bond had activity against three tumor cell lines and $IC_{50}$s of these compounds were 0.05, 0.06, and 0.06 ${\mu}mol/mL$ against three tumor cell lines, respectively. But these compounds had no antibacterial activity. $IC_{50}$s against U937 human histiocytic lymphoma cells were verified with the structural modification: $IC_{50}$s of 1, 2, 3, and 4 were 0.33, 0.06, 0.25, and 0.33 ${\mu}mol/mL$, respectively.

• Archives of Pharmacal Research
• /
• v.26 no.10
• /
• pp.861-867
• /
• 2003

Inhibitory effect of the lectins (KML-C) isolated from Korean mistletoe (KM; Viscum album coloratum) on tumor metastases produced by murine tumor cells (B16-BL6 melanoma, colon 26M3.1 carcinoma and L5178Y-ML25 lymphoma cells) was investigated in syngeneic mice. An intravenous (i.v.) administration of KML-C (20-50 ng/mouse) 2 days before tumor inoculation significantly inhibited lung metastases of both B16-BL6 and colon 26-M3.1 cells. The prophylactic effect of 50 ng/mouse of KML-C on lung metastasis was almost the same with that of 100 $\mu$ g/mouse of KM. Treatment with KML-C 1 day after tumor inoculation induced a significant inhibition of not only the experimental lung metastasis induced by B16-BL6 and colon 26M3.1 cells but also the liver and spleen metastasis of L5178Y-ML25 cells. Furthermore, multiple administration of KML-C given at 3 day-intervals after tumor inoculation led to a significant reduction of lung metastasis and suppression of the growth of B16-BL6 melanoma cells in a spontaneous metastasis model. In an assay for natural killer (NK) cell activity. i.v. administration of KML-C (50 ng/mouse) significantly augmented NK cytotoxicity against Yac-1 tumor cells 2 days after KML-C treatment. In addition, treatment with KML-C (50 ng/mouse) induced tumoricidal activity of peritoneal macrophages against B16-BL6 and 3LL cells. These results suggest that KML-C has an immunomodulating activity to enhance the host defense system against tumors, and that its prophylactic and therapeutic effect on tumor metastasis is associated with the activation of NK cells and macrophages.

• Molecular & Cellular Toxicology
• /
• v.5 no.2
• /
• pp.172-178
• /
• 2009

Nanoparticles are small-scale substances (<100 nm) with unique properties, complex exposure and health risk implications. Aluminum oxide ($Al_2O_3$) nanoparticles (NP) have been widely used as abrasives, wear-resistant coatings on propeller shafts of ships, to increase the specific impulse per weight of composite propellants used in solid rocket fuel and as drug delivery systems to increase solubility. However, recent studies have shown that nano-sized aluminum (10 nm in diameter) can generate adverse effects, such as pulmonary response. The cytotoxicity and genotoxicity of $Al_2O_3$ NP were investigated using the dye exclusion assay, the comet assay, and the mouse lymphoma thymidine kinase (tk$^{+/-}$) gene mutation assay (MLA). IC$_{20}$ values of $Al_2O_3$ NP in BEAS-2B cells were determined the concentration of 273.44 $\mu$g/mL and 390.63 $\mu$g/mL with and without S-9. However IC$_{20}$ values of $Al_2O_3$ NP were found nontoxic in L5178Y cells both of with and without S-9 fraction. In the comet assay, L5178Y cells and BEAS-2B cells were treated with $Al_2O_3$ NP which significantly increased 2-fold tail moment with and without S-9. Also, the mutant frequencies in the $Al_2O_3$ NP treated L5178Y cells were increased compared to the vehicle controls with S-9. The results of this study indicate that $Al_2O_3$ NP can cause primary DNA damage and cytotoxicity but not mutagenicity in cultured mammalian cells.

• Proceedings of the PSK Conference
• /
• 2003.04a
• /
• pp.177.1-177.1
• /
• 2003

Sophoricoside was isolated as the inhibitor of IL -5 bioactivity from Sophora japonica (Leguminosae). It has been reported to have an anti-inflammatory effect on rat paw edema model. To develope as an anti-allergic drug, genotoxicity of sophoricoside was investigated in bacterial and mammalian cell system such as Ames bacterial test and mouse lymphoma tk gene assay (MOLY). (omitted)

• Proceedings of the Korea Society of Environmental Toocicology Conference
• /
• 2003.05a
• /
• pp.183-184
• /
• 2003

Sophoricoside was isolated as the inhibitor of IL-5 bioactivity from Sophora japonica (Leguminosae). It has been reported to have an anti-inflammatory effect on rat paw edema model. To develop as an anti-allergic drug, genotoxicity of sophoricoside was investigated in bacterial and mammalian cell system such as Ames bacterial test, chromosomal aberration assay, Comet assay and MOLY assay. In Ames test, sophoricoside of 5000 ∼ 313 $\mu\textrm{g}$/plate concentrations was not shown significant mutagenic effect in Salmonella typhimurium TA98, TA100, TA1535 and TA1537 strains. The cytotoxicity (IC$\_$50/ and IC$\_$20/) of sophoricoside was determined above the concentration of 5000 $\mu\textrm{g}$/ml in Chinese hamster lung (CHL) fibroblast cell and L5178Y mouse lymphoma cell line. At concentrations of 5000, 2500 and 1250 $\mu\textrm{g}$/ml, this compound was not induced chromosomal aberration in CHL fibroblast cell in the absence and presence of S-9 metabolic activation system. Also in comet assay, DNA damage was not observed in L5178Y cell line. Also in MOLY assay, sophoricoside of 5000 ∼ 313 $\mu\textrm{g}$/ml concentrations was not shown significant mutagenic effect in absence of S-9 metabolic activation system. However, the higher concentration of 5000 and 2500 $\mu\textrm{g}$/ml of sophoricoside induced the increased mutation frequency (MF) in the presence of S-9 metabolic activation system. From these results, no genotoxic effects of sophoricoside observed in bacterial systems whereas, genotoxic effects observed in mammalian cell systems in the presence of metabolic activation system. These results suggested that the metabolite(s) of sophoricoside can cause some genotoxic effects in mammalian cells.

• Molecular & Cellular Toxicology
• /
• v.1 no.2
• /
• pp.99-105
• /
• 2005

Perchloroethylene (tetrachloroethylene, PCE), a dry cleaning and degreasing solvent, can enter ground-water through accidental leak or spills. PCE can be degraded to trichloroethylene (TCE), 1, 1-dichloroethylene (DCE) and vinyl chloride (VC) as potential bio-product. These compounds have been reported that they can cause clinical diseases and cytotoxicity. However, only a little genotoxic information of these compounds has been known. In this study, we investigated DNA single strand breaks of PCE, TCE, DCE and VC by single cell gel electrophoresis assay, (comet assay) which is a sensitive, reliable and rapid method for DNA single strand breaks with mouse lymphoma L5178Y cells. From these results, $37.5\;{\mu}g/ml$ of PCE, $189\;{\mu}g/ml$ of TCE and $56.4\;{\mu}g/ml$ of DCE were revealed significant DNA damages in the absence of S-9 metabolic activation system meaning direct-acting mutagen. And in the presence of S-9 metabolic activation system, $41.5\;{\mu}g/ml$ of PCE, $328.7\;{\mu}g/ml$ of TCE and $949\;{\mu}g/ml$ of DCE were induced significant DNA damage. In the case of VC, it was revealed a significant DNA damage in the presence of S-9 metabolic activation system. Therefore, we suggest that chloroethylene compounds (PCE, TCE, DCE and VC) may be induced the DNA damage in a mammalian cell.